The research program will consist of a series of integrated biochemical and morphological studies on the formation and removal of intracellular lipid deposits in rabbit arterial cells. Three projects are planned: 1) Cells freshly isolated from normal aorta will be used to develop differentiated, quiescent smooth muscle cell cultures which more closely reflect the physiologic state of arterial cells in situ. These cultures will be used for a general study of smooth muscle cell lipid metabolism. Attempts will also be made to induce cholesteryl ester accumulation in such cultured cells. 2) Lipid-laden atheromatous cells isolated from diseased aortas will be placed in culture. Cholesterol trapping agents will be added and the cellular excretion of cholesterol followed. At the same time, changes in the lipid content, enzyme activity, and morphological appearance of the cells will be assessed. 3) Mobilization of intracellular lipid deposits in atheromatous arterial cells in intact animals will be studied. Rabbits will be rendered atherosclerotic by feeding on a cholesterol diet for 3 months after which they will be placed on a regression regimen. At periodic intervals thereafter up to 2 years, (a) cells in the intact aorta will be studied by electron microscopy and (b) diseased cells isolated from such aortas will be analyzed for their lipid content, enzyme activities, and morphologic appearance as in project 2. Each project will be studied with the following methodology: biochemistry, including quantitative morphometry and cytochemistry.